In Vivo Animal Testing

One potential risk that formulators run when using cosolvents as drug solubilizers is the possibility of vehicle toxicity. Each cosolvent is characterized by an acceptable concentration range, which cannot be exceeded without incurring biological damage. To avoid the requirement for in vivo testing, several in vitro models have been advanced to evaluate the relative safety of cosolvent excipients. The most useful in vitro procedure follows the hemolysis of red blood cells, which has been correlated with in vivo animal tests [87,88]. 

The following in vitro tests, replacing in vivo animal tests, have been endorsed as scientifically valid by ECVAM and have been adopted as EU test methods (EU 2006) ... 

Whether a particular in vivo animal test is sufficient to establish usefulness of an invention in humans depends on determination of what is a standard test animal. In the Hartop case (8), the inventors, to demonstrate safety of a thiobarbiturate anesthetic composition, submitted rabbit test results coupled with evidence that rabbits were standard tests animals for this area. The court held the specification indicated that although human therapy was contemplated the rabbit tests were sufficient to prove usefulness of the composition for the inventors purpose. Tests under actual conditions of contemplated use—that is, in humans—were not required because one skilled in the art would accept the tests as indicating it to be reasonably certain that the invention would have the utility alleged. 

This backdrop sets the stage for in vitro testing because human tissues can be used and this type of surrogate may yield better predictive results than in vivo animal testing. Cytotoxicity or the measure of toxicity in cell culture is the most common in vitro method. Several end points for cytotoxicity tests have been developed. 

Finally, a battery of alternative testing models for neurotoxicity is not expected to fully replace current in vivo animal testing, but it would limit such testing only to those compounds for which, for different reasons, additional information on neurotoxicity is deemed important. Without concerted efforts by regulatory agencies, institutions, foundations, and private entities worldwide, it is doubtful that such a validation process will take place. If so, ten years from now, we will still be discussing perhaps new, sophisticated models, that have the potential to serve as screening tool for neurotoxicity, but that would leave this potential still unfulfilled. 

In contrast to the UHTSS, when assays using individual proteins or subcel-lular preparations are not appropriate to measure receptor binding or illicit a pharmacological response, more sophisticated cell-based or in vivo assays are necessary [11]. The speed at which individual compounds can be screened dramatically decreases in these systems, especially in the case of in vivo animal testing, where... 

Mention was made that animal studies have shown laetrile to be ineffective against cancer, but in vivo animal tests generally employ mice, which are simply different from the human animal, as are cattle, etc. And even human individuals vary because of biochemical individuality.)... 

Biological medicines require biological tests to ensure efficacy and safety. In-vitro tests are sufficient and in-vivo animal testing is required. Animal testing should be conducted in accordance with regulations. 

Synthetic hiomaterials, whether they are metallic, ceramic or polymeric, shall be thoroughly tested for their in vivo hiocompadbility. In vivo animal tests apparently place a burden on the shoulders of many materials-hased research groups since such animal tests require tedious histological examinations and careful interpretation. In vitro osteoblast cell culture tests, mainly reporting the live/dead cell numbers and the popular ALP (alkaline phosphatase) activity data, have thus been the most routine tests performed by the materials-based research groups which lack collaborative partnerships with the external veterinarians and skilled histologists. DMEM (or a-MEM) solutions are the media of choice in such in vitro cell culture tests. 

Experimental in vivo animal testing of the model of Branger and Eckmann [97], upon which the estimates of the time for dissolution of microbubbles in cerebral tissues are based, appear to validate the model. The model could be applied to various situations ranging from the dissolution of oxygen microbubbles in blood saturated... 

In Vivo Animal Tests of Hermetic-Encapsulating Coatings for Artificial Retina. 80... 

According to the results obtained using norms EN 30993-5, DIN UA 12, and in vivo animal tests reported in the literature, vitamin E and its products of oxydegradation are biocompatible and not cytotoxic [64—66]. 

Several in vitro tests are routinely used and accepted by regulatory authorities, but they present crucial limitations that affect the usefulness of the assays to predict mutagenicity/genotoxicity potential of a substance in vivo in mammals and especially in humans. Owing to these limitations, no single in vitro test can fully replace an existing in vivo animal test yet. 

---